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Procalcitonin behaves as a fast responding acute phase proteinin vivoandin vitro

Nijsten, Maarten W.N. MD; Olinga, Peter PhD; The, Hauw T. MD, PhD; de Vries, Elisabeth G.E. MD, PhD; Koops, Heimen Schraffordt MD, PhD; Groothuis, Geny M.M. PhD; Limburg, Pieter C. PhD; ten Duis, Henk J. MD, PhD; Moshage, Han PhD; Hoekstra, Harald J. MD, PhD; Bijzet, Johan; Zwaveling, Jan H. MD, PhD

Clinical Investigations
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Objectives: Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states. PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP). The source of production and its mechanism of induction are unknown. We investigated the inducibility of PCT bothin vivoandin vitroand compared the behavior of PCT with those of SAA and CRP.

Design: A prospective descriptive patient sample study and a controlled liver tissue culture study.

Setting: A university hospital.

Patients: Cancer patients who were treated with human tumor necrosis factor-α (rhTNF-α; 5 patients) or interleukin-6 (rhIL-6; 7 patients).

Measurements and Main Results: Serial serum samples were collected for analysis of concentrations of PCT, SAA, and CRP. In the TNF-α group, frequent sampling was performed on the first day to allow analysis of initial responses. In a human liver slice model, the release of PCT, SAA, and CRP was measured on induction with rhTNF-α and rhIL-6 for 24 hrs. We found that PCT displayed acute phase reactant behaviorin vivoafter administration of both rhTNF-α and rhIL-6. After rhTNF-α-administration, PCT reached half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA or CRP did. PCT, SAA, and CRP were produced in detectable quantities by liver tissuein vitro.PCT production by liver slices was enhanced after stimulation with rhTNF-α or rhIL-6; SAA and CRP concentrations were elevated after stimulation with rhTNF-α.

Conclusions: We found that PCT and acute phase proteins such as CRP are induced by similar pathways. The liver appears to be a major source of PCT production. Thus, PCT may be considered an acute phase protein. The different kinetics of PCT, rather than a fundamentally different afferent pathway, may explain its putative diagnostic potential to discriminate bacterial infection from other causes of inflammation.

From the Department of Surgery (Drs. Nijsten, ten Duis, and Zwaveling), the Department of Clinical Immunology (Dr. Hauw The), the Department of Medical Oncology (Dr. de Vries), the Department of Surgical Oncology (Drs. Schraffordt Koops and Hoekstra), the Department of Rheumatology (Dr. Limburg and Mr. Bijzet), and the Department of Gastroenterology and Hepatology (Dr. Moshage), University Hospital Groningen, and the Groningen Institute for Drug Studies, Department of Pharmacokinetics and Drug Delivery, University Centre of Pharmacy, University of Groningen (Drs. Olinga and Groothuis).

Supported, in part, by grants from Organon International NV and Solvay Pharmaceuticals BV.

Address requests for reprints to: Maarten W.N. Nijsten, Department of Surgery, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: m.w.n.nijsten@chir.azg.nl

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